[(2R,3R,4R,5R)-4-acetyloxy-5-(2-amino-6-oxo-1H-purin-9-yl)-2-[(4-oxo-1,3,2-benzodioxaphosphinin-2-yl)oxymethyl]oxolan-3-yl] acetate | 135942-87-9

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: [(2R,3R,4R,5R)-4-acetyloxy-5-(2-amino-6-oxo-1H-purin-9-yl)-2-[(4-oxo-1,3,2-benzodioxaphosphinin-2-yl)oxymethyl]oxolan-3-yl] acetate
• CAS: 135942-87-9
• 化学式: C₂₁H₂₀N₅O₁₀P
• 分子量: 533.391
• InChiKey: RLVHGRIOWXVZBC-MNDVXXFFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  37
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  192
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  [(2R,3R,4R,5R)-4-acetyloxy-5-(2-amino-6-oxo-1H-purin-9-yl)-2-[(4-oxo-1,3,2-benzodioxaphosphinin-2-yl)oxymethyl]oxolan-3-yl] acetate 在 三正丁胺 、 三丁基焦磷酸铵 、 sulfur 作用下， 生成 Acetic acid (2R,3R,4R,5R)-4-acetoxy-2-(4,6-dihydroxy-4,6-dioxo-2-thioxo-2λ⁵,4λ⁵,6λ⁵-[1,3,5,2,4,6]trioxatriphosphinan-2-yloxymethyl)-5-(2-imino-6-oxo-1,2,3,6-tetrahydro-purin-9-yl)-tetrahydro-furan-3-yl ester
  参考文献：
  名称：

  Synthesis of nucleoside 5'-O-(1,3-dithiotriphosphates) and 5'-O-(1,1-dithiotriphosphates)

  摘要：

  The synthesis of 3'-deoxy-3'-azidothymidine 5'-O-(1,3-dithiotriphosphate) (5) as the first example of a nucleoside 5'-O-(1,3-dithiotriphosphate) is described. 2-Chloro-4H-1,3,2-benzodioxaphosphorin-4-one phosphitylates the 5'-hydroxy group of 3'deoxy-3'-azidothymidine to form intermediate 1. Reaction of 1 with thiopyrophosphate (9) and sulfur results in the formation of an unseparable mixture of 3'-deoxy-3'-azidothymidine 5'-O-(1,3-dithiotriphosphate) (5) and 3'-deoxy-3'-azidothymidine 5'-O-(1,2-dithiotriphosphate) (3). Selective hydrolysis of 5 allows isolation of 3. However, reaction of 1 with P1-O-(cyanoethyl)-P1-thiopyrophosphate (8) and sulfur produced the diastereomers of 5 in good yield. Compound 8 is prepared by reaction of 3-hydroxyproprionitrile with 2-chloro-4H-1,3,2-benzodioxaphosphorin-4-one, pyrophosphate, and sulfur to yield 10, which is ring opened to 8 by reaction with ethylenediamine. Hydrolysis of this compound leads to 9. An alternative route to nucleoside 5'-O-(1,3-dithiotriphosphates) consists of reacting a nucleoside 5'-O-(1-thiocyclotriphosphate) such as 13 with Li2S. This reaction, when performed in pyridine/dioxane, leads to a mixture of the nucleoside 5'-O-(1,3-dithiotriphosphate) and the nucleoside 5'-O-(1,1-dithiotriphosphate). The latter is the only nucleotide product when the reaction is carried out in DMF.

  DOI：

  10.1021/jo00005a023
• 作为产物：
  描述：

  2-氯-1,3,2-苯并二氧磷杂环己烷-4-酮 、 2',3'-di-O-acetylguanosine 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.17h， 生成 [(2R,3R,4R,5R)-4-acetyloxy-5-(2-amino-6-oxo-1H-purin-9-yl)-2-[(4-oxo-1,3,2-benzodioxaphosphinin-2-yl)oxymethyl]oxolan-3-yl] acetate
  参考文献：
  名称：

  乙二胺合成α-P-修饰核苷二磷酸

  摘要：

  本报告描述了 α-P-硼烷-、α-P-硫代-和 α-P-硒修饰的核苷二磷酸类似物的一锅合成，否则很难获得。关键步骤涉及 5 中的氨基进行分子内亲核攻击以去除 γ-磷酸盐。P-非对映异构体的绝对构型通过其 1H NMR 分析得到证实。亲和力研究表明，核苷硼二磷酸在抗病毒研究中可能有用。

  DOI：

  10.1021/ja055179y

文献信息

• Synthesis and Separation of Diastereomers of Ribonucleoside 5‘-(α-P-Borano)triphosphates
  作者：Kaizhang He、Ahmad Hasan、Bozenna Krzyzanowska、Barbara Ramsay Shaw

  DOI：10.1021/jo972002g

  日期：1998.8.1

  synthesize the set of ribonucleoside (A, U, G, and C) 5'-(alpha-P-borano)triphosphates. Phosphitylation of the 2',3'-protected ribonucleoside with 2-chloro-4H-1,3,2-benzodioxaphosphorin-4-one gives the 5'-phosphite intermediate 2 which undergoes in situ substitution in the presence of pyrophosphate to give the cyclic intermediate, P(2),P(3)-dioxo-P(1)-ribonucleosidylcyclotriphosphate 3. Immediate oxidation

  核苷硼酸磷酸酯（其中一个磷酸氧原子被一个硼烷基团取代）是天然核苷酸的等离子和等电子类似物。硼酸磷酸酯也是硫代磷酸酯和甲基膦酸酯的生物化学重要同系物。我们已经开发了一种方便的一锅法来合成5'-（α-P-硼烷）三磷酸核糖核苷（A，U，G和C）的集合。2'，3'-保护的核糖核苷被2-氯-4H-1,3,2-苯并二氧杂磷酰基-4-酮进行磷酸化，得到5'-亚磷酸酯中间体2，该中间体在焦磷酸盐存在下进行原位取代，从而得到环状中间体，P（2），P（3）-二氧代-P（1）-核糖苷基环三磷酸酯3。用胺。硼烷络合物立即氧化化合物3产生核糖核苷5' -（α-P-硼烷）环三磷酸酯4。随后将化合物4与水反应，然后使其与氢氧化铵反应，得到的粗产物为核糖核苷5'-（α-P-硼烷）三磷酸酯6的非对映异构体混合物。分离出纯化合物6。使用离子交换色谱法可得到30-45％的总收率。通过反相HPLC分离核糖核苷5'-（α-P-硼烷）三磷酸酯6的两个非对映异构体。
• Stereospecific synthesis of guanosine 5'-O-(1,2-dithiotriphosphates)
  作者：Janos Ludwig、Fritz Eckstein

  DOI：10.1021/jo00020a029

  日期：1991.9

  The synthesis of the four diastereomers of guanosine 5'-O-(1,2-dithiotriphosphate) by two different approaches is described. 2',3'-Diacetylguanosine is phosphitylated with 2-chloro-4H-1,3,2-benzodioxaphosphorin-4-one to form 2, which upon reaction with S-2-cyanoethyl phosphorothioate and sulfur forms 3. Subsequent hydrolysis of this intermediate produces the two diastereomers of guanosine 5'-O-(1,2-dithiodiphosphate) (GDP-alpha-S-beta-S, 4). These can be phosphorylated by both acetate or pyruvate kinases. The R(p)R(p) as well as the S(p)R(p) diastereomers of guanosine 5'-O-(1,2-dithiotriphosphate) (GTP-alpha-S-beta-S, 5) can be obtained by reaction of (R(p))- or (S(p))-GDP-alpha-S-beta-S, respectively, with acetate kinase. Pyruvate kinase only accepts (S(p))-GDP-alpha-S-beta-S as substrate and therefore only (S(p)S(p))-GTP-alpha-S-beta-S is available by this route. All four diastereomers of GTP-alpha-S-beta-S can be synthesized by the second approach, in which 2 is reacted with thiopyrophosphate to produce a mixture of the diastereomers of GTP-alpha-S-beta-S and of guanosine 5'-O-(1,3-dithiotriphosphate) (GTP-alpha-S-gamma-S). The latter is removed by selective hydrolysis and subsequent chromatography. The four diastereomers of GTP-alpha-S-beta-S can be separated by HPLC according to their configuration at P-alpha into two groups consisting of the S(p)S(p)/S(p)R(p) and the R(p)S(p)/R(p)R(p) diastereomers. Glycerol kinase selectively hydrolyzes the diastereomers with the R(p) configuration at P-beta, thus making (S(p)S(p)- and (R(p)S(p)-GTP-alpha-S-beta-S available from the two groups. Myosin is stereospecific for reaction with diastereomers with the S(p) configuration at P-beta, allowing the isolation of the S(p)R(p) and R(p)R(p) diastereomers. P-31 NMR spectroscopy of the Cd2+ salts of the four diastereomers reveals two groups of complexes, which differ in their P-alpha-beta coupling constants which can be related to the arrangement of the guanosine and the gamma-phosphate as either cis or trans in the six-membered cyclic complex.
• Rapid and efficient synthesis of nucleoside 5'-0-(1-thiotriphosphates), 5'-triphosphates and 2',3'-cyclophosphorothioates using 2-chloro-4H-1,3,2-benzodioxaphosphorin-4-one
  作者：Janos Ludwig、Fritz Eckstein

  DOI：10.1021/jo00264a024

  日期：1989.2